tbuckley/cabot-search huggingface dataset:
PB2135: TREATMENT PATTERNS IN PATIENTS WITH NEWLY DIAGNOSED AL AMYLOIDOSIS
Authors: Anita D’souza, Tiffany Quock, Ansgar Conrad, Michael S Broder, Ashis K. Das, Eunice Chang, Marian H. Tarbox
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Treatment options for AL amyloidosis remain limited. Aims: To describe current patterns of medication use in patients with newly diagnosed AL amyloidosis. Methods: This retrospective analysis used 2017-2020 data from the Merative® MarketScan® Commercial and Medicare Supplemental and the IQVIA Pharmetrics Plus® databases to identify adult patients (newly diagnosed) with ≥1 inpatient or ≥2 outpatient claims for AL amyloidosis (ICD-10-CM code E85.81) in any diagnosis field during the identification period (1/1/2018-12/31/2020). The first observed AL amyloidosis diagnosis date was the index date. Continuous enrollment in a health plan during the 1 year before (baseline) and ≥3 months after (follow-up) index was required. Patients with an AL amyloidosis diagnosis during the baseline period or who received no treatment were excluded. Study outcomes included demographic/clinical characteristics and treatment patterns. We reported on lines of treatment, duration (defined as continuous use from first line to end of days’ supple without a gap of ≥120 days), and adherence (proportion of days covered, PDC, ≥80% while persistent) to first-line therapy. Results: The final sample consisted of 338 patients with newly diagnosed AL amyloidosis. Mean (SD) age at diagnosis was 61.2 (9.1) years and 42.3% of patients were female. As the first-line therapy, 72.5% patients received bortezomib-containing regimens, whereas only 13.9% received daratumumab-containing regimens. The most common first-line treatment was bortezomib-cyclophosphamide-dexamethasone (34.0%), with mean (SD) duration of 138.7 (100.9) days and mean (SD) PDC of 98.4% (5.8%). Overall, for patients with first-line treatment (except for hematopoietic stem cell transplant [HSCT]), the mean (SD) duration was 143.2 (136.7) days, mean (SD) PDC was 0.978 (0.064), and 97.2% were adherent (PDC ≥80%). For patients with second-line treatment, the most common was HSCT (23.4%), followed by bortezomib-daratumumab-dexamethasone and daratumumab alone (both 11.1%). Summary/Conclusion: Bortezomib-containing regimens were the most common first-line therapy and HSCT was the most common second-line therapy. Even though treatment availability is limited for AL amyloidosis, newly diagnosed patients in this study were highly adherent to their first-line therapy. Additional therapies for AL amyloidosis are currently under development. Keywords: Treatment, Bortezomib, AL amyloidosis, Real world data
PB2013: THE FREQUENCY, EVOLUTION AND SIGNIFICANCE OF GENE MUTATION IN MYELODYSPLASTIC SYNDROMES WITH NORMAL KARYOTYPE
Authors: Feng Xu, Lingyun Wu, Zheng Zhang, Qi He, Juan Guo, Chunkang Chang, Xiao LI
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: Large-scale sequencing of MDS reveals that gene mutations play important roles in driving the occurrence of MDS, however, little is known about the features of mutations in MDS patients with normal karyotype. Aims: To analyze the gene mutations characteristics and significance for MDS patients with normal karyotype. Methods: 36 genes (high frequency in MDS) were chosen as an assembly to perform the target sequencing for 352 MDS patients with normal chromosome, comparing to 268 cases with abnormal chromosomes. Results: We found that the mutation frequency reached 81.2% for the 352 cases, without difference for the initial mutations (ASXL1, DNMT3A or TET2) when compared to controls. And rare special chromosome-related gene mutations were defined, such as TP53, RUNX1 and U2AF1. Moreover, 20 out of the 352 cases underwent repeated sequencing while the AML transformation did not occur. 14 of them showed mutation evolution, with, or without clinical progression. Finally, 25 MDS/AML (secondary AML) patients accepted paired sequencing analysis between the diagnostic point and immediately after AML transformation. 20 paired samples were defined with newly emerged (15 cases) or existed (5 cases) transformation related mutations (active signaling, transcription factors and tumor suppressor). Summary/Conclusion: High frequency gene mutations, together with the mutation evolution before and after AML transformations, suggested the diagnostic significance of target sequencing for those MDS suspected individual with normal karyotype. The frequency, evolution and significance of gene mutation in myelodysplastic syndromes with normal karyotype *Correspondence to: Xiao Li, MD, PhD, Dept. of Hematology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. E-mail: [email protected], Tel: +86-021-24058745, F-Fax: +86-021-64701361 This study was supported by the National Natural Science Foundation of China (Grant No. 81770120 and 81770122) The authors declare no competing financial interests. Keywords: MDS, Mutation
PB2100: REAL-WORLD TREATMENT PATTERNS OF TRIPLE-CLASS REFRACTORY (TCR) MULTIPLE MYELOMA (MM) ACROSS THE UNITED STATES (US), CANADA, AND WESTERN EUROPE: A RETROSPECTIVE CHART STUDY
Authors: Xavier Guillaume, Dahbia Horchi, Jorge Gomez, Patrick Hlavacek, Jinma Ren, Alex Schepart, Didem Aydin, Marco Dibonaventura
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Many patients with MM relapse or become refractory to various therapeutic approaches and typically cycle through many lines of treatment. Aims: The present study sought to understand how patients with TCR MM (ie, refractory to ≥1 PI, ≥1 IMiD, and ≥1 anti-CD38 therapy) are managed across various countries. Methods: A non-interventional, retrospective chart review study was conducted across the US, Canada (CA), the UK, France (FR), Germany (DE), Italy (IT), and Spain (ES). Oncologists/hematologists were recruited to abstract medical chart information into an electronic case report form from eligible MM patients (eg, refractory to ≥1 IMiD, ≥1 PI, and ≥1 anti-CD38 antibody treatment, ECOG≤2, and initiated their first therapy after their TCR status [ie, their index therapy] between 1/1/2018 and 12/31/2020 to ensure at least 1 year of follow-up). Abstractions were performed from January through April 2022. Demographics, clinical characteristics, and treatment patterns were descriptively analyzed and reported here. Results: N=314 patients with TCR MM were included (56.7% male; median age=70). Clinical characteristics were similar to other TCR MM studies (eg, 26.1% had an ECOG score of 2, 25.8% had high cytogenetic risk (ie, t(4:14), t(14:16), and/or del(17p), and 10.2% had extramedullary disease). Patients received a median of 3 treatment lines prior to their index therapy, with 70 unique treatment regimens reported as part of their index therapy line (Table 1). The most common regimens (>10%) were Pd and Kd. Summary/Conclusion: This global chart review across the US, Canada, and Western Europe highlights the consistent lack of a standard of care for the management of MM among patients who are refractory to the three main classes of therapies.Keywords: Treatment, Multiple myeloma, Real world data, Myeloma
PB2097: CLINICAL IMPLICATION OF CYTOGENETIC ABERRATIONS IN NON-AL AMYLOIDOSIS MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A MULTI-CENTER CHINESE CASE SERIES
Authors: Yang Liu, Yueyun Lai, Qiang Yang, Hongyu Zhang, Jia Feng, Liru Wang, Lei Wen, Wenbing Duan, Lu Gao, Xuelin Dou, Ling MA, Jin Lu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Reports on cytogenetic aberrations in non-AL amyloidosis-monoclonal gammopathy of renal significance (MGRS) and their impact on treatment efficacy are rare. Aims: Describing case series of patients with renal biopsies-proved non-AL amyloidosis-MGRS receiving bortezomib based clone-directed therapies. Methods: We retrospectively reviewed patients’ data from three hematological centers in China. The clinical characteristics, genetic information and renal outcome were analyzed. Results: Thirty-one patients were subjected to CD138 MACS-fluorescence in situ hybridization (FISH). Twenty-three cases (74.2%) harboured cytogenetic aberrations by magnetic sorting FISH. IgH translocations’ frequency was 61.3% and t(11;14) (q13;q32) accounted for 38.7% (Figure). After first line bortezomib-based treatment, among 21 patients with baseline dFLC (difference between involved and uninvolved serum free light chain level) more than 20 mg/L or SPEP (serum protein electrophoresis) more than 10 g/L, 11 achieved complete response (CR) or very good partial response (VGPR) or low-dFLC response. 9/11 VGPR + CR + low-dFLC response in the non-t (11;14) group while 3/10 achieved VGPR in the t (11;14) group (p = 0.084, Fisher test). According to ISA criteria, renal response was achieved in 15/18 in the non-t (11;14) group vs 3/11 in the t (11;14) group (p = 0.005). The 24h-UTP decreased by a median of 20% in the t (11;14) group and 74.1% in non-t (11;14) group (p = 0.005). Patients without t (11;14) showed a trend of eGFR improvement compared to the t (11;14) group.Summary/Conclusion: 61.3% non-AL-type amyloidosis-MGRS patients had IgH recombination, with t (11;14) (q13; q32) the most common. Patients with t (11;14) may have inferior renal responses to bortezomib-based treatment. Keywords: Multiple myeloma
PB2240: TREATMENT OUTCOME OF CHRONIC MYELOMONOCYTIC LEUKEMIA; A SINGLE CENTRE EXPERIENCE FROM PAKISTAN
Authors: Nida Anwar, Naveena Fatima, Zoya Ziad, Laraib Majeed, Tahir Shamsi
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Chronic myelomonocytic leukemia (CMML) is an uncommon clonal hematopoietic disease characterized by an increase in monocytes and dysplasia of myeloid progenitor cells classified as myelodysplastic/myeloproliferative neoplasm (MDS/MPN). The accumulated clinical information and laboratory data on CMML demonstrate the development of the disease’s diagnosis and therapy. Aims: The study was conducted to observe the outcome of CMML patients in the stratified groups according to CMML type, karyotype and treatment. Methods: A cross sectional study was conducted at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi Pakistan from 2018-2022. Approval from the Institutional ethics committee was obtained prior to the study. Baseline investigations were done and clinical parameters were recorded. Bone marrow biopsy samples were taken and stained by leishman stain. Cytogenetic analysis was performed on overnight, 24-h un-stimulated and 72-h stimulated bone marrow cultures using standard procedures. Descriptive statistics were reported by using SPSS version 23.0 Results: A total of 29 CMML patients were analyzed, median age was 63(28-85) years with male predominance (62%). MPN type was more prevalent 25(86%), 22(76%) patients had normal karyotype and 12(41%) were CMML-0 as per WHO classification. Overall Cytarabine was given in 8(28%) patents with MPN type, azacytidine to 2(7%) patients with MDS type and decitabine was offered to 13(52%) patients with MPN type and only a single MDS type patient received decitabine. Total deaths were observed in 14(44%) patients out of which 12(86%) had MPN type. Groups on the basis of CMML type, treatment and karyotype were stratified and deaths, post treatment infection and transfusion dependency were evaluated in each stratified group and no significant association (P value >0.05) was observed. The association of CMML type with the post treatment infections was found significant and it revealed that MPN type had more post treatment infections than MDS type (P value =0.042). Summary/Conclusion: This was one of the first studies conducted on CMML Pakistani patients and it was observed that although there was no significant association among the treatment groups yet decitabine was given in majority of MPN type subgroup and post treatment infections were prevalent. Further longitudinal studies with follow up data along with the integration of NGS for risk stratification would be a noteworthy addition. ` Keywords: Treatment, CMML
PB1854: EARLY SEVERE ADVERSE EVENTS OF ACUTE MYELOID LEUKEMIA THERAPY DEPENDING ON THE INDUCTION THERAPY REGIMEN
Authors: Evgeniy Mikhailov, Ekaterina Smolyakova, Saglai Khertek, Maksim Granatkin, Anastasiya Popova, Evgeniy Boguraev, Vadim Doronin
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: New targeted therapy allows conducting effective therapy for acute myeloid leukemia (AML), including cases of elderly and frail patients. However, the early mortality rate remains at a high level and, basing on different resources, can reach up to 30%. The primary problem of induction therapy of AML is infectious complications. We assessed the frequency of neutropenic fever, sepsis development and hospitalization to intensive care unit (ICU) among patients with AML in the first 8 weeks of the therapy. Aims: To assess the incidence of sepsis, ICU hospitalizations and deaths among patients with AML depending on the option chosen for induction therapy regimen Methods: This retrospective study includes 135 patients with newly diagnosed AML during the period of 2020-2023. The median age was 62 years (range 18-90 years), 54,1% females, 45,9% males. 51,8% of the patients receiving intensive chemotherapy (7 + 3 ±FLT3 inhibitors), 48,2% of patients received low-intensity venetoclax-containing protocols (combined with hypomethylating drugs or low-dose cytarabine). Sepsis was defined in accordance with the Sepsis-3 criteria. The evaluated parameters included the rate of developing neutropenic fever, sepsis and hospitalizations to the Intensive Care Unit within the first 8 weeks from the AML treatment initiation. In all the patients, informed consent was obtained. Results: The groups of patients did not differ by gender, somatic status or risk group. Patients receiving venetoclax-containing regimens were significantly older (log rank p < 0.001), with a median age of 72 years, whereas among patients who received intensive therapy median age made up 51 years. Patients who received intensive chemotherapy had a significantly higher incidence of neutropenic fever (90% vs 43%, log rank p<0,0001, hazard ratio=4,042; 95% confidence interval 2.594-6,297), sepsis (40% vs 15,4%, log rank p=0,0057, hazard ratio=2,524; 95% confidence interval 1.309-4,864) and required ICU hospitalization more frequently (25,7% vs 12,3%, log rank p=0,0468, hazard ratio=2,185; 95% confidence interval 1.011-4,723). The median of overall survival was not reached in the group of patients treated with 7 + 3, while the median of overall survival was 54 months among patients treated with low-intensity therapy (log rank p=0,0436) Summary/Conclusion: Infectious complications still remain the main problem in the treatment of AML patients. Venetoclax-containing regimens result in lower rates of sepsis and associated ICU hospitalizations. However, the overall survival rate among patients receiving venetoclax-containing regimens is significantly lower.Keywords: Acute myeloid leukemia, Febrile neutropenia, Complications, Sepsis
PB2239: ACQUIRED VON WILLEBRAND DISEASE (AVWD) DIAGNOSTIC PROFILE IN MYELOPROLIFERATIVE NEOPLASIA (MN) PATIENTS IN WESTERN-ESTONIA
Authors: Ines Vaide, Virge Aabrams, Edward Laane
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Myeloproliferative diseases (MD) patients have the complication in both side of hemostasis - related to bleeding and thrombosis. Reducing thrombosis risk, major impact on morbidity and mortality is a major goal of therapy. However, in lifelong evaluating quality of life during the disease course, the bleeding has also important role. Acquired von Willebrand disease (AvWD) may result from increased proteolysis together with platelet activation, which leads to reduced von Willebrand factor activity (vWFact). Aims: We analysed our MD patient cohort to lab analysis related to hemostatsis to better understand the patients profile. Methods: Chart review of the two Medical Centers case records with diagnosis of D47.3, D45 and D47.1 between years 2016-2021. Results: During 2016-2022 in total 145 patients with MD where in regular follow-up in both Centers. Patients with essential thrombocythemia (ET) consisted of 35.17%, with polycythemia vera (PV) of 33,79% and with primary myelofibrosis (PMF) of 31,03%. In 58 patients the analysis of von Willebrand factor antigen (vWFAg), vWFact, Factor 8 were measured in case of bleeding tendency or before operation and invasive procedures. Semiautomated von Willebrand factor multimer assay was performed in 53 patients. AvWD was diagnosed in 13 from 23 with ET, in 5 from 14 with PMF and in 3 from 12 patients with PV diagnosis. In all patients except two the vWFact/vWFAg ratio was below 0.7 and the multimeric assay shows decreased high molecular weight of multimers and in two ratio was normal but decreased high molecular weight of multimers at the same time. 7 patients died during the observation period, 3 of them from thrombosis, 1 from bleeding and 1 from thrombosis together with bleeding related courses. Summary/Conclusion: AvWD can be a complication of patients with ET, PV and PMF. We recommend VWF Ag and vWF act testing during course of disease and before planned surgical intervention or invasive procedures to diagnose potential AvWD. Keywords: Myeloproliferative disorder, Acquired von Willebrand syndrome
PB2404: ASSOCIATION OF P14ARF EXPRESSION WITH THE RISK OF PROGRESSION AND DEATH IN DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Maria Sarpova, Elena Vaneeva, Dmitry Diakonov, Vitaliy Rosin, Svetlana Samarina, Sergei Gritsaev
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: The p14ARF protein that encoded in the CDKN2A locus of the 9p21 chromosomal region is the participant in the p14ARF-Hdm2-p53 signaling pathway. It is able to regulate cell cycle arrest and/or apoptosis in both p53-dependent and independent ways. In a normal cell, protein is maintained at a low level. The increase of p14ARF expression is noted in cancer cells and it helps the stabilization of p53 protein, although its protooncogenic property is not excluded. It is assumed that the p14ARF protein may be a potential predictor of unfavorable outcome in patients with diffuse large B-cell lymphoma (DLBCL). Aims: To define the association of p14ARF protein expression in tumor cells with the risk of progression and death in DLBCL patients. Methods: The formalin-fixed paraffin embedded samples of tumor tissue of 104 patients with newly diagnosed DLBCL were included to the study. All patients received first-line R-CHOP therapy. The median age of the examined patients was 59 years (Q1-Q3:49–67 years). Samples were evaluated using an Axio Scope.A1 microscope (Carl Zeiss, Germany). Expression of p14ARF was studied using a morphometric method. The software (Russia) was used for statistical data processing. Results: p14ARF-positive tumor cells were found in 88 (84.6%) patients. The maximum relative number of p14ARF-positive cells was set at 96%, the median was 76% (Q1-Q3:22-84). Patients divided into groups according to clinical and laboratory parameters (over 60/under 60 years of age, high/normal serum lactate dehydrogenase concentration, the presence of more/no more than one extranodal lesion, non-GCB/GCB immunohistochemical subtype) didn’t differ significantly in the number of p14ARF-expressing cells at the time of diagnosis of the disease (Mann-Whitney U test). According to univariate analysis of the Cox proportional hazards model the rise by every 10% of p14ARF-positive tumor cells is associated with the increase of the risk of disease progression by 14% (p = 0.009; HR = 1.014, 95% CI = 1.004-1.025) and the risk of death by 19% (p = 0.003; HR=1.019; 95% CI=1.006-1.033). Summary/Conclusion: The increasing of the number of p14ARF-expressing tumor cells is associated with an increased risk of progression and death in patients with DLBCL. This factor can be considered as a potential predictor of progression-free and overall survival but further studies are warranted. Keywords: Diffuse large B cell lymphoma, Protein Expression, Survival
PB2093: OVERALL SURVIVAL IN RELAPSED-REFRACTORY MYELOMA PATIENTS DEPENDS ON CIRCULATING PLASMA CELLS QUANTITATION
Authors: Nunziatina Laura Parrinello, Grazia Scandura, Sara Marino, Anna Triolo, Vittorio Del Fabro, Francesco DI Raimondo, Concetta Conticello, Alessandra Romano
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: There is a growing interest in investigating the clinical impact of circulating clonal plasma cells (CCPC) quantitation reflecting the tumor burden in multiple myeloma (MM), due to its easy access and non-invasive nature. Recent studies have highlighted the value of quantification of CCPC at diagnosis for risk stratification of transplant eligible and not MM. However, prospective data on the real-world utility of CCPC quantitation in relapsed-refractory patients (RRMM) treated with novel immunotherapies is extremely scarce. Aims: To investigate the prognostic value of CCPC quantitation in treated with novel immunotherapies using high-sensitivity multicolor-flowcytometry (HS-MFC) and the relevance of their assessment in predicting overall survival (OS). Methods: We prospectively evaluated 44 consecutive MM patients requiring first salvage regimen containing daratumumab from July 2018 through July 2021 (age: median-65 years; range-44-81 years; M/F-30/14). CCPC levels were studied using 10-13 color HS-MFC (sensitivity- 0.0001% or 1x10e- 6) at the start of the salvage regimen. CCPC levels were calculated as CCPC percentages in total WBCs (%CCPC/WBC). The cut-off value was identified using ROC analysis against OS. Initial therapeutic response (ITR) was monitored at the end of the second cycle of treatment. Results: The median follow-up was 46 months (range 1-51 months). ITR included CR-VGPR 6.5%, VGPR/PR-63.0%, SD-21.7%, and 4 (8.7%) patients died during initial therapy. CCPCs were detected in all patients. Median %CCPC/WBC was 0.41% (range, 0.004-6%). CCPCs from patients with higher LDH and extra-medullary disease carried significant lower amount of CD27 and CD81 and higher amount of CD200 although no difference in the percentage of CCPCs was recorded. %CCPC/WBC ≥0.4% was strongly associated with OS (27.1 months vs 48.5; HR-2.5; p=0.04). Conclusion: This prospective study showed that CCPC quantification (≥0.4% of WBC) at start of daratumumab-based salvage regimen in RRMM patients treated at the first relapse provides a powerful independent biomarker for the prediction of OS. Such assessment is more convenient for routine clinical practice and should be confirmed in larger studies.Keywords: Survival prediction, Multiple myeloma, Plasma cells